This invention concerns new vaccines developed using recombinant DNA technology to provide useful immune responses in circumstances where traditional vaccines may not be sufficiently effective.
Many existing live or killed vaccines are not without disadvantages, often significant, in respect of, for example, high production costs, poor response, low response to poorly immunogenic antigens, instability and a requirement for adjuvants. Furthermore, alternative vaccine preparations based on agents such as purified proteins or synthetic peptide antigens frequently offer only poor protection. In response to these problems, attention has turned to the development of vaccines in which recombinant DNA methods have been used to introduce antigens to which immunity is required, into carrier viruses such as vaccinia.
The advantage of the recombinant DNA approach is that an infectious recombinant virus simultaneously synthesises the foreign polypeptide and viral antigen, which can then be delivered to a host immune system as a superficial skin lesion. Vaccinia viruses have, for example, been modified for expression of the genes for hepatitis B, human immunodeficiency virus, influenza and malaria antigens; the construction of recombinant viruses carrying other antigens of medical or veterinary importance is under investigation.
In some instances, however, the immune response of recombinant vaccines may be of limited nature and magnitude. Thus, while peripheral immunisation with vaccinia-influenza recombinants provides good protection against lower respiratory tract infection, it fails to induce immunity in the upper respiratory tract. On the other hand, peripheral immunisation with recombinant vaccines may prove ineffective when local rather than systemic immunity is required, as in say the gastro-intestinal tract.
There have been various attempts to remedy these deficiencies, including expression of vaccine antigens through viruses having stronger promoters, such as poxvirus, but to date these have not met with significant success. The present invention provides an effective means for enhancing the immune response to the specific foreign antigenic polypeptides of recombinant vaccines.
The immune system is regulated in part by molecules, known as lymphokines, which are released by lymphocytes and help or modify the functions of other classes of lymphocytes. The present invention is based on a recognition that the expression of appropriate lymphokines from recombinant bacterial or viral vaccines can boost and/or modify the immune response to viral, bacterial or co-expressed foreign antigenic polypeptides.